In Vivo Imaging of the Islets of Langerhans

Abstract

The islets of Langerhans play a central role in maintenance of glucose homeostasis. Apoptosis of the insulin-producing beta cells of the islet leads to diabetes mellitus. The ability to non-invasively image or assess the islets of Langerhans would yield valuable insight into the progression of diabetes, guiding interventions intended to slow or halt diabetes progression and enabling assessment of islets after transplantation. The primary objective of this dissertation was to establish and validate a technique capable of non-invasively imaging the islet of Langerhans. The bulk of this work focuses on the use of bioluminescence imaging. Islets were engineered to express the luciferase optical reporter gene and applied to murine models of diabetes and transplant settings. In order to accurately quantify information from in vivo bioluminescence imaging, light-emitting standards were employed to determine sources of variance and standardize measurements. A three-dimensional bioluminescence reconstruction algorithm was characterized using these light-emitting standards and applied to bioluminescent islets. As bioluminescence imaging is limited to small animal models, clinically relevant islet imaging approaches using magnetic resonance imaging and target contrast agents were evaluated.